The basic objective of this proposal is to study an aspect of endocrine interaction, namely: the mechanism(s) by which ACTH reduces plasma testosterone (T) levels. ACTH depresses plasma T in normal men without a decrease in LH levels, and plasma T is suppressed in men following surgery at a time when LH is elevated. Under the stress of surgery, spermatic venous levels of T are decreased in male dogs. This suggests that the male dog may be a good model for studying the action(s) of ACTH in depressing plasma T levels. We plan to use the male dog, therefore, to determine whether ACTH acts directly on the testes to inhibit T synthesis and secretion, or whether its effect on plasma T levels is adrenal mediated. A combination of direct and an adrenal mediated action may be involved. Both in vivo and in vitro experiments will be used to explore these questions. The in vivo experiments will: 1) determine whether the effect of ACTH on T levels is a direct one at the testicular level or an adrenal mediated one; 2) determine the effect of ACTH on the metabolic clearance rate (MCR) of T. The in vitro experiments will: 1) characterize the steroidogenic processes in canine dispersed Leydig cells; 2) determine the specific point(s) at which ACTH interferes with T secretion.